The Danish-Norwegian randomized trial on beta-blocker therapy after myocardial infarction: Design, rationale, and baseline characteristics.

AIM: The evidence for beta-blocker therapy after myocardial infarction (MI) is randomized trials conducted more than 30 years ago, and the continued efficacy has been questioned. DESIGN AND METHODS: The ongoing Danish (DANBLOCK) and Norwegian (BETAMI) randomized beta-blocker trials are joined to evaluate the effectiveness and risks of long-term beta-blocker therapy after MI. Patients with normal or mildly reduced left ventricular ejection fraction (LVEF≥40%) will be randomized to open-label treatment with beta-blockers or no such therapy. This event-driven trial will randomize ∼5700 patients and continue until 950 primary endpoints have occurred. As of July 2023, 5228 patients have been randomized. Of the first 4000 patients randomized, median age was 62 years, 79% were men, 48% had a STEMI, and 84% had a normal LVEF. The primary endpoint is a composite of adjudicated recurrent MI, incident heart failure, coronary revascularization, ischemic stroke, all-cause mortality, malignant ventricular arrhythmia, or resuscitated cardiac arrest. The primary safety endpoint includes a composite of recurrent MI, heart failure, all-cause mortality, malignant ventricular arrhythmia, or resuscitated cardiac arrest 30 days after randomization. Secondary endpoints include each of the components of the primary endpoint, patient-reported outcomes, and other clinical outcomes linked to beta-blocker therapy. The primary analysis will be conducted according to the intention-to-treat principle using a Cox proportional hazards regression model. End of follow-up is expected in December 2024. CONCLUSION: The combined BETAMI-DANBLOCK trial will have the potential to affect current clinical practice for beta-blocker therapy in patients with normal or mildly reduced LVEF after MI.

Impact of Male-Origin Microchimerism on Cardiovascular Disease in Women: A Prospective Cohort Study.

Increasing parity is associated with an increased risk of ischemic heart disease (IHD) and stroke in women. This is probably attributable to biological responses of pregnancy. Male cells of presumed fetal origin are commonly present in women years after pregnancy-a phenomenon termed male-origin microchimerism (MOM). In this study, we investigated whether MOM was associated with risk of IHD and ischemic stroke in women. We evaluated the association between MOM and ischemic events in a cohort of 766 Danish women enrolled in the Diet, Cancer and Health cohort during 1993-1997 when aged 50-64 years. Of these women, 545 (71.2%) tested positive for MOM through targeting of the Y chromosome (DYS14 DNA sequence) in their blood. Multiple Cox regression models were used to calculate hazard ratios with 95% confidence intervals. We found that MOM was associated with a significantly reduced rate of IHD (hazard ratio = 0.44, 95% confidence interval: 0.23, 0.83) but not ischemic stroke (hazard ratio = 0.80, 95% confidence interval: 0.46, 1.41). Our findings show that microchimerism positivity is associated with a lower rate of later IHD development in women. Although the underlying mechanisms are presently unknown, MOM may be relevant in women's cardiovascular health. More studies are needed to confirm these findings.